Our long term objective is the treatment of cardiac arrhythmia in the ambulatory patient by automatic infusion of antiarrhythmic drugs from an implanted pump. The rationale for this approach is that existing therapies are not satisfactory for many patients with paroxysmal tachycardias. Inefficacy, delay in response , inconvenience, and side effects are serious flaws with existing therapies. As an alternative solution, we propose a system which infuses antiarrhythmic drugs when an arrhythmia is present. The system operates "closed-loop" by following a cyclic sequence of tachycardia detection, drug delivery, tachycardia re-evaluation, and readjustment of drug delivery. In the previous project period, we developed a system which detects atrial fibrillation and delivers a pharmacokinetically-based infusion of procainamide or disopyramide. We tested non-implantable models of this system in dogs and patients during provocative electrophysiologic studies. We implanted a miniaturized version of the system in a dog and repeatedly demonstrated detection of induced atrial fibrillation and termination with disopyramide over a period of one month. With technical feasibility now established our goal is to have a device for human implantation ready for clinical trials by the conclusion of the proposed project period. We will design and develop such a device and perform detailed bench and animal tests. Concurrently, we will perform extensive clinical evaluation of the technique ex vivo. Our specific aims are to: 1) design and manufacture a device for human implantation which incorporates arrhythmia detection and drug delivery in a single unit and which permits external programming and status communication; test the device by implanting it in a series of dogs in which atrial fibrillation can be induced. 2) integrate the electrophysiologic amplifiers, intravenous pump, and personal computer used in our feasibility studies into a portable, stand-alone instrument which can detect atrial fibrillation at bedside and which can deliver a pharmacokinetically-based infusion of procainamide; validate the concept of, and obtain parameters for, the implantable closed-loop device by using this beside instrument in surgical intensive are with patients who have paroxysmal atrial fibrillation subsequent to cardiac surgery. 3) design and test a technique for individualizing pharmacokinetically-based infusion, during electrophysiology study in patients. The specific aim of this project will be achieved through an effort which combines engineering design and implant development at the Pritzker Institute of Medical Engineering of the Illinois Institute of Technology with animal and clinical studies at the Pritzker School of Medicine of The University of Chicago.